Changes to Individual Effectors, part 2
= Skin = Schematic of Sympathetically Innervated Structures in Skin Denervation Patterns The effect of thoracic sympathectomy is to produce two distinct areas of skin, one denerved and the other still innervated. Over a two year period (2004-2005), Songboy1234 conducted a survey of the skin denervation patterns of 37 ETS patients. The method was simple. The patients were asked, “Which parts of your body still sweat, and which parts don’t?” Also noted was which version of ETS surgery had been performed. Two patterns of skin denervation were found, Pattern I and Pattern II. Below are the results. Comparison of Cutaneous Denervation Patterns for Different ETS Variations Surgery involving T2 (by itself or with other levels) was significantly more likely to cause full-blown, pattern I corposcindosis (100% vs. 43%). More data of skin denervation patterns are sought. ETS surgeons are called upon to ask the same simple questions and publish their findings. Sweat Glands Anhidrosis Sweat glands are controlled almost entirely via the sympathetic nervous system, and do not have parasympathetic innervation at all. Unlike most other sympathetic nerve terminals, the receptors in sweat glands are activated by acetylcholine, not norepinephrine. It is possible that sweat glands can be activated locally to a small degree by catecholamines in the blood, but for practical purposes sympathectomy renders sweat glands permanently non-functional in the denerved area. This dysfunction is called "anhidrosis". Anhidrosis is considered dangerous, as we learn from the WebMD dictionary: Anhidrosis: Not sweating. From the Greek an- meaning a lack of + hidros meaning sweat = lack of sweat. The inability to sweat may seem a blessing but it is not, since to sweat is to be able to stay cool. Anhidrosis creates a dangerous inability to tolerate heat. (WebMD dictionary) In one clinical trial, ETS patients subjectively described the sensation of anhidrosis as “disturbing”. “Patients undergoing T2-T4 resection often experience anhidrosis from the nipple line upwards which has been disturbing for several individuals.” (Fischel et al. 2003) The disturbing, dry, hot sensation of anhidrosis can be severe enough to require the frequent application of hand lotion. As shown below, the extreme dryness can develop into a form of eczema (see Niinai et al. 2004) Eczema on the Hands After ETS Surgery Pathologic Gustatory Sweating (Frey’s Syndrome) A strange symptom of corposcindosis is “gustatory sweating”, properly known as Frey’s Syndrome. Rare in nature, this is common and well-documented after ETS surgery, usually manifesting many months after surgery. Upon eating or smelling certain foods, particularly those that are sour or spicy, the patient can experience tingling or sweating sensations along the arms, in the forehead, or other denerved areas. Classic Frey’s Syndrome is caused by injury to or near the parotid (saliva) glands, below and in front of the ear. The mechanism by which ETS surgery causes Frey’s Syndrome is unknown. This is puzzling. How can olfactory stimulation trigger upper-body sweating, when exercise and hot temperatures cannot? ETS patient and discussion board administrator “Elaine” aka “Aubrey”, has offered this: “(Gustatory Sweating after ETS) is caused by aberrant nerve regeneration. Messages to salivate cross with messages for sweating, flushing and goosebumps.” (Elaine 2004) Though the mechanism is not known, clearly olfactory sensation somehow is able to active sympathetic activity in the denerved region. If we could understand the mechanism, perhaps we could harness it and re-establish sympathetic tone where corposcindosis patients so desperately desire it. I call for research. Patients should be warned about gustatory tingling and sweating. Arrector Pili Muscles – Goose Bumps As a defense against cold temperatures, and more importantly in response to certain emotional stimuli, the control center can increase sympathetic tone on arrector pili muscles. The tiny muscles contract, which pulls the skin down in little patches, leaving the remaining patches raised, thus forming “goose bumps”. This increases the total surface area of the skin. Greater surface area means better insulation, so core body heat will escape more slowly. The thermoregulatory effects of goosebumps are minimal, and some consider this effect to be a vestigial artifact inherited from our hairier mammalian ancestors. However, the emotional importance of goosebumps to humans cannot be overlooked. Emotions such as fear, sexual arousal, pride, awe, nostalgia and joy can trigger strong goose bumps. This can be accompanied by a physically pleasurable sensation that some describe as “nearly orgasmic”. A strong neural signal is sent from the control center down to the base of the spinal cord, where it branches off, left and right, into the lumbar regions of the sympathetic chains. It begins traveling upwards in a wave, branching off into each sympathetic ganglion, stimulating goose bumps and physical pleasure in each innervated region, while continuing up the chain. Eventually it reaches the thoracic ganglia, which deliver the signals to the arrector pili in the neck. This gives rise to the expression “making the hairs on the back of the neck stand up”, a phenomenon observed in all mammals. Finally, the wave will descend down the arms and around the scalp, completing the process that may last several seconds. Many people find this experience profoundly pleasurable and satisfying. Entire websites have been dedicated to extolling the pleasure and emotional satisfaction derived from goose bumps. = Muscles = Recall the discussion of blood flow changes after ETS. Loss of sympathetic tone diminishes release of Nitric Oxide, which in turn diminishes vasodilation in skeletal muscles during exercise. This might be expected to then alter muscle composition in some way. “After interruption of sympathetic activity, a change in muscle fiber composition of the rabbit masseter muscle was observed. These changes consisted in atrophic and hypertrophic fibers, fiber splitting, necrosis and phagocytosis, and fibrosis. It was postulated that these changes in fiber types were due to redistribution of blood flow resulting from sympathectomy”. (Hashmonai 2003) (See also Papa et al. 1986) Atrophic and hypertrophic mean decreasing and increasing in size respectively. Necrosis means cell death. Phagocytosis is a process wherein a cell surrounds and ingests a bacteria or other object. Fibrosis is the forming of scar tissue. Considering these very important discoveries in rabbits, human study of the effects of ETS on muscle composition is clearly in order. Patients should be warned of possible changes to muscle composition, based on animal data and the Hashmonai postulate. = Sensory Nerves = Loss of Tactile Sensitivity The anecdotal oral histories consistently report loss of tactile sensitivity in the denerved areas. Is this possible, given that sensory nerves are something separate from sympathetic nerves? Yes, because “sympathetic nerves are known to modulate sensory nerve function” (Merhi et al. 1998; see Khalil 1997). Back in the 1940’s, surgeons were using sympathectomy to treat a number of war-related problems, including causalgia. Causalgia is a burning pain sensation resulting from injury to sensory nerves, usually in the arms or legs. To begin figuring out if sympathectomy would be effective, the surgeons first injected anesthetic into the sympathetic ganglion. “The prompt relief of pain after the injection the sympathetic ganglion was usually striking and conclusive” (Freeman 1955). This led the surgeons to use sympathectomy, both thoracic and lumbar, to alleviate pain. The war surgeons had provided empirical confirmation for the physiological discoveries later made by Merhi, Khalil and colleagues: that the SNS has a strong role in the modulation of sensory nerves. Mailies and Furlan conducted a 2002 review of sympathectomy in the treatment of pain syndromes. As Mailis explains, today “many neuropathic pain syndromes, particularly reflex sympathetic dystrophy and causalgia (currently called Complex Regional Pain Syndromes (CRPS), types I and II, respectively), are thought to be ’Sympathetically Maintained Pain’.” (Mailis et al. 2002) Pain Now let’s apply the principle of denervation super-sensitivity to the receptor cells in the sensory nerves. After they are denerved, it is expected that they will become super-sensitive to catecholamines. We can surmise that super-sensitivity induced on a sensory nerve would manifest as “pain”. Mailis again: “Furthermore, complications of surgery may be significant, in terms of both worsening the pain or producing a new pain syndrome. . .” (Mailis et al. 2002, emphasis added) Mailis concludes “more clinical trials of sympathectomy are required to establish the overall effectiveness and potential risks of this procedure.” (Mailis et al. 2002). I too call for research into the role of the SNS in modulating sensory nerves, and the effect of ETS on sensitivity. Patients should be warned about potential loss of tactile sensitivity in the denerved area, and possible chronic nerve pain. Paresthesia Loss of sympathetic drive to sensory nerves may also manifest as parestheia, which is experienced as a tingling or burning sensation. 17.6% of patients reported permanent paresthesia in a 2005 Chinese study. Paresthetic discomfort distinguishable from wound pain was described by 17 patients (50.0%). The most common descriptions were of 'bloating' (41.2%), 'pins and needles' (35.3%), or 'numbness' (23.5%) in the chest wall. The paresthesia resolved in less than two months in 12 patients (70.6%), but was still felt for over 12 months in three patients (17.6%). Sihoe et al. 2005 = Adipose Tissue = Lipogenesis and Lipolysis Weight gain and loss of energy are common anecdotal complaints found in the oral history, so we turn now to the study of fat tissue. Mammals have two types of fat tissue, White Adipose Tissue (WAT) and Brown Adipose Tissue (BAT). WAT is located primarily under the skin surface and serves to store energy, and as a layer of insulation against the cold. BAT is found in deeper nooks and crannies, and is a prime source of generating heat energy (thermogenesis). BAT will be discussed in the section on thermoregulation. The control center maintains homeostasis in adipose by altering energy intake and energy expenditure. WAT is able to store excess energy when food is abundant, and make that energy available when food is scarce. WAT stores energy in the form of molecules called lipids. Each individual white adipose cell can shrink or grow, depending on whether lipids are being burned or deposited. The size of the fat cell is known simply as “Fat Cell Size” or FCS. The body can also create new fat cells, and we can count them and call that “Fat Cell Number” or FCN. Lipogensis is the deposition of fat. It is accomplished by depositing more lipid in each cell, increasing the FCS; and by creating brand new adipose cells, increasing the FCN. Lipolysis is the chemical decomposition and release of fat from adipose tissue, otherwise known as “burning fat”. Cross Section of White Adipose Tissue Robert Bowers, head of the Molecular and Cellular Biology and Pathobiology Program, at the Medical University of South Carolina, heads up a world-wide research team studying the metabolism of adipose tissue. Bowers and colleagues warn that “Prolonged positive energy balance promotes obesity that in humans is associated with a number of health risks. The deposition of lipid initially results in increases in fat cell size (FCS), but soon triggers increases in fat cell number (FCN)” (Bowers et al. 2004, see also Satcher 2001) “The accretion of lipid in and of itself is not necessarily associated with these health risks (see Simms 2001); rather it is the distribution of body fat that is critical (see Gasteyger et al. 2002). That is, visceral obesity is closely associated with development of the “metabolic syndrome” and type II diabetes (see Vague 1980). Thus understanding how body fat is preferentially deposited and mobilized is necessary for the prevention and treatment of obesity, respectively.” (Bowers et al. 2004) Could ETS surgery affect adipose metabolism? If so, how? To begin answering, we first ask, “Does the SNS run to adipose tissue?” Yes, it does. “White adipose tissue (WAT) is innervated by the sympathetic nervous system (SNS)”. (Bowers et al. 2004). Brown adipose is also sympathetically innervated, and will be discussed under thermoregulation. . The sympathetic nervous system evidently plays a dominant role in the regulation of fat burning, and adipose function in general. In their 1994 study of lypolysis burning in humans, researchers at University College London stated: “Catecholamines are powerful regulators of lypolysis. In both in vivo and in vitro studies, stimulation of adrenoreceptors in adipose tissue (from at least some sites) dominates over alpha 2-adrenoreceptor inhibition of lipolysis. Catecholamines may reach adipose tissue via the general circulation or via the rich sympathetic innervation”. (Coppack et al. 1994) Back in the 1990’s, the London researchers observed, “It is apparent that lipolysis is controlled largely by sympathetic activity and insulin concentrations.” (Coppack et al. 1994) By 2004, consensus had become even clearer, allowing Bowers to state unequivocally in his introduction, “Although the more established role of this sympathetic innervation of WAT is as a major stimulator of lipid mobilization, this innervation also inhibits WAT fat cell number (FCN); thus, local sympathetic denervation of WAT leads to marked increases in WAT mass and FCN.” (Bowers et al. 2004) The purpose of Bowers’ study then is just to further quantify what is already known. Bowers shares our suspicions about this dominant role of the SNS: “One mechanism that may underlie the differential accumulation of lipid by WAT depots, as well as the differential mobilization of lipid, is through its innervation by the sympathetic nervous system (SNS) and the effects of its primary postganglionic neurotransmitter, norepinephrine (NE)”. (Bowers et al. 2004). All of this allows the CS model to generate two more predictions about thoracic sympathectomy in humans: Sympathectomy and Adipose Tissue To satisfy his curiosity, Bowers and colleagues set about doing sympathectomies on hamsters. The results? “Sympathetic denervation produced significant increases in WAT mass and FCN” (Bowers et al. 2004). Below are graphs summarizing their findings. “R” WAT and “I” WAT refer to adipose tissue in two different body locations. “R” stands for “retroperitoneal”, which means in the abdominal cavity, “I” stands for “inguinal” which means in the groin area. Mass of White Adipose Tissue in Innverated vs. Sympathetically Denervated Hamsters Number of White Adipose Cells in Innervated vs. Sympathetically Denervated Hamsters (iWAT) Number of White Adipose Cells in Innervated vs. Sympathetically Denervated Hamsters (rWAT) Clearly, sympathectomy caused a great increase in the mass, the size and the number of fat cells in these mice. The denervation of white adipose tissue produced by ETS surgery will likely follow the same patterns as the skin, since a good deal of it is located directly under the skin. Pattern I corposcindosis then would entail sympathetic denervation all the WAT from the chest upwards. It would also lower the catecholamine levels in the blood, as shown earlier. Thus both sources of lypolysis stimulation, neural and hormonal, will be affected by ETS surgery. However, most of the body’s adipose lies below the chest, and would remain innervated, and potentially hyperactive. We call for study of the effects of ETS surgery on lipolysis and lipogenesis in humans. Based on animal studies and the anecdotal oral history, there is compelling reason to do so. Until then, ETS remains experimental with regard to adipose. Patients should be warned as such and informed of the likely effects, based on theory and animal data. In the early 1990’s some very important discoveries were made about fat metabolism – the discovery of the ob (obesity) gene, and of “leptin”. Leptin is a peptide released by adipose tissue into the blood stream. Leptin will travel to the hypothalamus and bind with receptors there. Thus, leptin acts as another input to the control center. Sufficient leptin in the blood tells the control center “enough storing of fat”. There is a great deal of interest in leptin studies currently, because mice given extra leptin lose a lot of body fat. However, great caution is in order, because not only does leptin have a key role in the regulation of fat metabolism, it turns out to be essential to bone metabolism as well.